Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholic (ASH) and nonalcoholic (NASH) steatohepatitis show an almost identical morphology. Since the clinical picture is not characteristic, liver biopsy is still the diagnostic gold standard. ASH and NASH are morphologically characterized by a combination of steatosis, hepatocellular injury (ballooning degeneration, apoptosis, necrosis), perivenular and pericellular fibrosis, and inflammation (mostly neutrophils). A definitive differentiation of ASH and NASH is only possible by exclusion of alcohol abuse. Although NASH comprises a syndrome with a multifactorial etiology, adipositas seems to be the most constant associated causal factor. The pathogenesis of both diseases is still unclear. Clinical evidence and experimental studies suggest an important toxic role of reactive oxygen species (oxidative stress). According to our experience, ballooning of hepatocytes is a constant morphologic feature of ASH and NASH and already present in the early stages of disease. Ballooned cells often (but not always) contain Mallory bodies (alcoholic hyalin), which are irregular cytoplasmic inclusions consisting of keratins and nonkeratin components, including ubiquitin. Ballooning is associated with a disturbance and finally almost disappearance of the keratin-intermediate filament cytoskeleton. In our studies on the pathogenesis of ASH and NASH, we concentrated on these cytoskeletal alterations and Mallory body formation. It could be shown that in the early stages overexpression and hyperphosphorylation of keratins take place. Moreover, the 1:1 ratio of keratin type I (keratin 18) and type II (keratin 8) necessary for the assembly of intermediate filaments is disturbed and the equilibrium shifted toward keratin 8. Thus, the pool of soluble keratin 8 increases. The resulting keratin monomers are sensitive to misfolding and either degraded or aggregated as inclusion bodies. If the proteolytic capacity is impaired (e.g., by inhibition of the proteasomal system) in the chronically stressed cell aggregation prevails,finally leading to Mallory body formation. Convincing evidence exists on the basis of clinical and experimental studies that keratins exert a nonskeletal protective function in simple epithelia (e.g., liver cells). Disturbance of the keratin system may thus significantly contribute to cell damage.
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PMID:[Alcoholic and nonalcoholic steatohepatitis. Histopathologic and pathogenetic considerations]. 1176 38

Alcohol abuse is associated with increases in both the incidence of fractures and complications in fracture healing. The purpose of this study was to determine the dose-dependent effects of ethanol on bone repair in a rat model. Three-month-old male Wistar rats were continuously fed liquid diets containing ethanol as either 36% or 26% of total calories or control diets for 6 weeks. Then, a bone repair model was created in all rats. Bone healing and liver metabolism were evaluated 7 weeks after bone injury. For each dose, there were three ethanol-feeding groups receiving (1) ethanol for 13 weeks, (2) control diet for 13 weeks (pair-fed), and (3) ethanol before bone injury and control diet (pair-fed) after injury. Another group was fed ethanol (36%) before injury and given control diet ad libitum after injury. There were also two nutritional controls consuming control diet and standard rat chow ad libitum for 13 weeks. Abnormal liver metabolism was evident at the higher ethanol dose - increases in cytochrome P4502E1 specific activity (5-fold; P < .01), triglyceride content (4-fold; P < .02), and liver weight (25%; P = .05) - compared with pair-fed controls. The higher dose of ethanol resulted in deficient bone repair when compared with rats receiving ethanol-free control diet by pair-feeding: 26% less (P = .02) rigidity of the repaired bone, 41% less (P = .02) intrinsic stiffness, 24% less intrinsic strength (P = .05), and 14% less (P = .001) ash density of the repair tissue. The reduced food consumption of ethanol-fed rats compared with that in the nutritional controls did not contribute to this deficiency. Furthermore, removal of ethanol (as 36% of calories) from the diet after bone injury completely restored normal bone healing and nearly normalized the liver metabolism. The lower ethanol dose (26% of calories) had a minimal effect on liver metabolism and bone repair. We conclude that ethanol (as 36% of calories) in the rat diet, especially during the postinjury period, was solely responsible for the observed inhibition of bone repair.
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PMID:Inhibition of bone repair in a rat model for chronic and excessive alcohol consumption. 1637 62

Alcohol abuse is a risk factor for bone fractures. Following a fracture, alcoholics have a higher risk for impaired fracture healing. However, the specific alcohol-induced defect(s) in bone healing are not known. Alcohol is a potent inhibitor of bone formation during bone growth and turnover. Thus, the purpose of this study was to determine the effects of alcohol consumption on induction of new bone formation. Demineralized allogeneic bone matrix (DABM) cylinders were used to model osteoinduction in a rat model for chronic alcohol abuse. DABM cylinders, prepared from femurs and tibiae of rats fed a normal diet, were implanted into sexually mature male rats adapted to alcohol (ethanol contributed 35% of caloric intake) or control liquid diets. Food intake in the control rats was restricted to match food intake of alcohol-fed animals. The implants were recovered 6 weeks later and analyzed by histology, muCT and chemical analysis. Histological evaluation revealed a robust osteoinductive response, resulting in mature bone ossicle formation, in DABM implants in rats fed the control diet. Alcohol consumption affected bone mass and architecture of the DABM implants but not volumetric density or mineral composition. Specifically, alcohol consumption resulted in significant decreases in DABM-induced bone volume, bone volume/mg original cylinder weight, connectivity density, trabecular number and thickness, ash weight and % ash weight. There were no changes in mineral (ash) density nor in the relative amounts of calcium, magnesium, iron, selenium and zinc (microg/mg ash), indicating that alcohol consumption did not impair mineralization. Taken together, these results show that alcohol abuse resulted in decreased bone formation within the DABM implant. We conclude that reduced osteoinduction may contribute to impaired bone healing in alcoholics.
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PMID:Impaired osteoinduction in a rat model for chronic alcohol abuse. 1756 49

Fatty liver disease is a multifactorial world-wide health problem resulting from a complex interplay between liver, adipose tissue and intestine and initiated by alcohol abuse, overeating, various types of intoxication, adverse drug reactions and genetic or acquired metabolic defects. Depending on etiology fatty liver disease is commonly categorized as alcoholic or non-alcoholic. Both types may progress from simple steatosis to the necro-inflammatory lesion of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH), respectively, and finally to cirrhosis and hepatocellular carcinoma. Animal models are helpful to clarify aspects of pathogenesis and progression. Generally, they are classified as nutritional (dietary), toxin-induced and genetic, respectively, or represent a combination of these factors. Numerous reviews are dealing with NASH animal models designed to imitate as closely as possible the metabolic situation associated with human disease. This review focuses on currently used mouse models of NASH with particular emphasis on liver morphology. Despite metabolic similarities most models (except those with chemically or genetically induced porphyria or keratin 18-deficiency) fail to develop the morphologic key features of NASH, namely hepatocyte ballooning and formation of histologically and immunohistochemically well-defined Mallory-Denk-Bodies (MDBs). Although MDBs are not universally detectable in ballooned hepatocytes in NASH their experimental reproduction and analysis may, however, significantly contribute to our understanding of important pathogenic aspects of NASH despite the obvious differences in etiology.
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PMID:Animal models of NAFLD from the pathologist's point of view. 2974 20

Alcohol and high-fat diet are two major risk factors responsible for metabolic diseases, which are manifested as steatohepatitis and liver cancer in the liver, and chronic pancreatitis and pancreatic adenocarcinoma (PDAC) in the pancreas. These metabolic diseases are becoming increasingly prevalent around the globe, and more importantly, their two major etiologies commonly coexist to precipitate the disease processes. To highlight the importance of these metabolic diseases, Japanese Society of Gastroenterology (JSGE) and National Institute on Alcoholism and Alcohol Abuse of National Institute of Health cosponsored the JSGE's 7th International Forum jointly held with the 12th International Symposium on ALPD and Cirrhosis. Toward the main theme of "Frontiers in ASH, NASH, NBNC-HCC and PDAC", this platform showcased presentations by 12 invited international and Japanese speakers on brain-gut-liver interactions, emerging mechanisms of ASH and NASH, metabolic reprogramming, and new therapeutic targets for cirrhosis, HCC, and PDAC. This editorial discusses the most recent data on global statistics on how alcohol and obesity impact health and longevity as a prelude to a brief summary of the symposium presentations and discussions, primarily focusing on the first two session themes.
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PMID:Alcoholic and non-alcoholic steatohepatitis: global perspective and emerging science. 3064 81